A recent study published on March 19, 2025, reveals that the addition of the mTOR inhibitor rapamycin during the cryopreservation of ovarian tissue significantly enhances fertility restoration in mice. This groundbreaking research by a team led by Dr. Bindels from the University of Liège demonstrates a potential new approach for fertility preservation in young women who undergo chemotherapy.
The study aimed to address a critical issue faced by many female cancer patients: the loss of ovarian function due to cancer treatments. Currently, one method available for preserving the fertility of prepubertal girls and young women is the cryopreservation of ovarian tissue followed by autotransplantation. However, this technique often results in substantial follicular loss, a phenomenon known as follicular burn-out, immediately after transplantation. In their previous research, the authors had noted that rapamycin could counteract this follicle activation. The current study tested and confirmed these findings in an in vivo model.
In this study, forty female C57BL/6 mice underwent unilateral oophorectomy, after which their ovaries were frozen using two different methods: one group used rapamycin in the freezing medium, while the other did not. After chemically inducing ovarian failure in the mice and then performing autotransplantation, the researchers monitored estrous cycles and mating outcomes over a four-month period.
Results showed a significant difference between the two groups. Mice whose ovaries were cryopreserved with rapamycin gave birth to more pups than those whose ovaries were frozen without the drug—102 live births compared to just 48. The live birth rate was also significantly higher in the rapamycin group, with a rate of 67.7% compared to 41.7% in the control group (P = 0.0025). Furthermore, more females in the rapamycin group gave birth, with 13 successful pregnancies compared to 8 in the control group. Although the average litter size was higher in the rapamycin group, this difference was not statistically significant.
Moreover, the study found that a greater number of primordial follicles remained in the ovaries of the rapamycin-treated mice at the end of the experiment compared to the control group (P = 0.0397), indicating that rapamycin effectively preserved this critical reproductive resource. However, the researchers did not observe any significant effects from rapamycin on oocyte quantity, as the number of oocytes collected during superovulation was comparable between the two groups.
The issue of ovarian cyst formation, which could potentially complicate future pregnancies, was also examined. While rapamycin did not affect the rate of cyst formation, the presence of ovarian cysts correlated with a reduced number of pups born per dam and lower live birth rates in both groups, highlighting the complex interplay between infertility and ovarian health. Notably, female mice without ovarian cysts tended to have larger litters, reinforcing prior research linking cyst presence to fertility outcomes.
This study underscores the promise that rapamycin may hold in improving fertility restoration methods for young cancer survivors. The findings suggest a potential clinical application for human patients undergoing fertility preservation prior to cancer treatment, providing a possible new pathway to enhance their chances of successful pregnancies post-treatment. The use of rapamycin during the ovarian cryopreservation process could pave the way for improved techniques that prevent ovarian damage and loss of fertility.
As cancer survival rates continue to improve due to advancements in treatment, preserving fertility for young survivors is becoming an increasingly important consideration. While the results are promising, the authors caution that further studies are needed to ensure the safety and efficacy of rapamycin application in clinical settings. Future research should focus on understanding the long-term effects of rapamycin on oocyte health and the overall reproductive potential of offspring born from treated grafts.